The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their pioneering work in Drosophila that elucidated the molecular mechanisms controlling circadian rhythm.

Self-assembly of synthetic molecules in living cells can influence cell function, but is extremely challenging due to the complex environment of cells. Here the authors report the self-assembly of small organic molecules that locate, target and self-report their supramolecular behavior in living cells.

The ability to spectroscopically pinpoint whether nanoparticles are located inside or outside of cells represents an overarching need in biology and medicine. Here, the authors show that the chirality of DNA-bridged particle dimers reverses when they cross the cell membrane, providing a real-time chiroptical signature of their intra- or extracellular location.

Integrating group IV lasing devices into technologically relevant CMOS architectures has proven challenging. Here, the authors demonstrate low-threshold lasing, which is important for potential electronic and photonic circuits, using strained germanium nanowires as the gain material.

Vibrational excitations are a fingerprint of molecule–surface interactions, but knowing how they scale across materials is tricky. Here, the authors discover correlations between the vibrational frequencies of adsorbates on transition metals, developing a predictive theory to allow interpretation of complex experimental spectra.

Cells of the fungus Rhizopus microsporus contain Burkholderia endobacteria that control its asexual reproduction. Here, the authors show that the endobacteria also mediate mating of the fungal host by modulating expression of a GTPase central to fungal reproductive development.

The cytokines IL-1β and IL-6 mediate the systemic acute phase response (APR). Here, the authors provide evidence that these cytokines lead to both synergistic and antagonistic gene expression during APR; synergistic induction occurs by assisted loading of STAT3 on chromatin by NF-κB.

Tailoring the thermodynamics of metal-hydrogen interactions is crucial for tuning the properties of metal hydrides but remains difficult to control. Here, the authors create an yttrium hydrogen sensor sensitive to pressure changes of up to four orders of magnitude by adding zirconium into the Y lattice.

Evolution of resistance is a common cause of cancer treatment failure and tumor progression. Here, the authors present a method for integrating evolutionary principles based on adaptive therapy into abiraterone therapy for metastatic castrate-resistant prostate cancer and show the positive results of an interim analysis of a trial cohort.

Quantum error correction plays a key role in quantum information and metrology, but generally requires complex gates and measurements sequences. Here, the authors use trapped ions to implement a scheme in which always-on coupling to an engineered environment protects the qubit against errors.

Parkin is an E3 ubiquitin ligase involved in Parkinson’s disease. Parkin has also been linked to cancer suppression but the mechanisms are unclear. Here the authors show that Parkin regulates HIF-1α through ubiquitin-dependent degradation, thus inhibiting metastasis of breast cancer cells.

Centromeres and large-scale structural variants evolve and contribute to genome diversity during vertebrate speciation. Here Ichikawa et al perform de novo long-read genome assembly of three inbred medaka strains, and report long-range structure of centromeres and their methylation as well as correlation of structural variants with differential gene expression.

The genesis of large igneous provinces (LIPs) remains controversial. Here, the authors examine the water contents of picrites from the Emeishan LIP and find that despite high water contents, the elevated temperature and trace elements suggest a mantle plume from a hydrous deep reservoir rather than subduction zone related.

The Bronze-age Indus civilisation (4.6–3.9 ka) was thought to have been linked to the development of water resources in the Himalayas. Here, the authors show that along the former course of the Sutlej River the Indus settlements developed along the abandoned river valley rather than an active Himalayan river.

Senescent cells can promote tumour progression through the activation of a senescenceassociated secretory phenotype (SASP). Here, the authors show that SASP activation is associated with non-cell autonomous cell transformation and tumour initiation in an in vivo model of adamantinomatous craniopharyngioma.

Neural crest cells arise within the central nervous system, then migrate and contribute to a variety of cell types. Here, the authors use multiplex transcript analysis at single cell resolution to define neural crest and neural subpopulations within the avian neural tube, including a neural crest stem cell niche.

The organic material κ-H3(Cat-EDT-TTF)2 has been suggested to exhibit a quantum spin liquid phase in which quantum fluctuations prevent the formation of magnetic order. Here, the authors show that this may be a result of fluctuations of hydrogen atoms, rather than more conventional geometric frustration.

Spectral reflectance has been used to achieve label-free, in vivo imaging of myelin, a membranous sheath that allows faster electrical conduction along neuronal axons. Here the authors extend this technique to measure nanoscale features, including changes following traumatic brain injury.

Changes in chromatin structure have been linked to organismal ageing. Here the authors show that altered histone expression and mitochondrial stress during C. elegans development result in chromatin changes and a cytosolic stress response that affects organismal longevity, and depends on HSF-1 and the chromatin remodeller, ISW-1.

Sleep in mammals comprises physiologically and functionally distinct stages. Here, the authors report a transitional sleep stage in Drosophila associated with 7–10 Hz oscillatory activity that can be obtained through activation of the sleep-promoting neurons of the dorsal fan-shaped body.

Adults adjust their cognitive performance according to the value of the outcome, but it is unclear whether adolescents do too. Here, authors show that adolescents do not adjust their cognitive effort according to value, and that this ability is mediated by connectivity between the striatum and prefrontal cortex.

The roles played by bactofilins, a widespread type of bacterial cytoskeletal elements, are unclear. Here, the authors show that the bactofilins BacNOP facilitate proper subcellular localization of the ParABS chromosome segregation system in the model organism Myxococcus xanthus.

Direct measurement of edge transport in the quantum anomalous Hall effect can be made difficult due to the presence of parallel conductive paths. Here, Mahoney et al. report features associated with chiral edge plasmons, a signature of robust edge states, by probing the zero-field microwave response of a magnetised disk of Cr-(Bi,Sb)2Te3.

Break-induced replication (BIR) is a double-strand break repair pathway that can lead to genomic instability. Here the authors show that the absence of Srs2 helicase during BIR leads to uncontrolled binding of Rad51 to single-stranded DNA, which promotes the formation of toxic intermediates that need to be resolved by Mus81 or Yen1.

Macrophage metabolism controls differentiation and subsequent adaptive immune responses. Here the authors show that mitochondrial membrane protein Fam73b regulates TLR-mediated mitochondrial switching of fusion to fission to induce IL-12 production via accumulation of Parkin and stabilization of IRF1 in macrophages, resulting in control of anti-tumor immunity in mice.

Large electronics limit low-noise, non-invasive electrophysiological measurements to a thousand simultaneously recording channels. Here the authors build an array of 65k simultaneously recording and stimulating electrodes and use it to sort and classify single neurons across the entire mouse retina.

Histone deacetylase (HDAC) inhibitors, a class of cancer therapeutics, cause thrombocytopenia via an unknown mechanism. Here, the authors show that HDAC6 inhibition impairs proplatelet formation in human megakaryocytes, and show that this is linked to hyperacetylation of the actin-binding protein cortactin.

The extracellular matrix is under variable strain, but we lack the tools to detect differences in strain. Here the authors develop a probe based on a bacterial fibronectin-binding peptide that binds to relaxed fibronectin fibrils and detects relaxed matrix in cell culture, tissue slices and in vivo.

The development of spin field effect transistors has been hampered by the low magnetoresistance in the semiconductor spin valve. Here the authors report large and tunable magnetoresistance in a lateral 2DES-based spin valve geometry due to finite electric field effects at the ferromagnet-semiconductor interface.

Temperature is known to influence plant disease development. Here Huot et al. show that elevated temperature can enhance Pseudomonas syringae effector delivery into plant cells and suppress SA biosynthesis while also finding a temperature-sensitive branch of the SA signaling pathway in Arabidopsis.

Vps34 is a lipid kinase conserved from yeast to humans and involved in in intracellular vesicular trafficking and autophagy. Here Bilanges et al. show that inhibition of this kinase in mice improves glucose tolerance and diet-induced steatosis by modulating mitochondrial respiration and metabolism.

SUMO and ubiquitin are key signal transducers in several cellular processes including the DNA-damage response. Here the authors describe a method for selective enrichment of ubiquitin substrates for E3 ligases from complex cellular proteomes and identify the SUMO conjugation machinery as direct RNF4 substrates.

TRAF6 is a RING E3 ligase that builds Lys63-linked ubiquitin chains. Here, the authors present the crystal structure of TRAF6 bound to the Ubc13~Ub conjugate, which, together with biochemical assays, reveals the role of the zinc finger domains and why RING dimerisation is required for TRAF6 activity.

Autoantibodies are found in neuropsychiatric conditions but without clear cellular mechanism and disease relevance. This study shows higher prevalence of autoantibodies against NMDAR receptors in schizophrenia patients, and patient-associated antibody can alter synaptic receptor trafficking and plasticity.

Long noncoding RNAs (lncRNAs) are key regulators of lineage specification during development. Here, the authors investigate remodeling of enhancers and regulation of the lncRNA transcriptome during mesendoderm specification, and identify a pluripotent stage-specific transcribed enhancer controlling adoption of the mesendodermal cell fate.

Mechanosensitive Piezo channels are important for a wide range of mechanotransduction processes. Here the authors show that Piezos interact with sarcoplasmic /endoplasmic-reticulum Ca2+ ATPases (SERCA) and give mechanistic insights into mechanogating and SERCA2-mediated regulation of Piezo1.

Rod photoreceptors are thought to be saturated under bright light. Here, the authors describe the physiological parameters that mediate response saturation of rod photoreceptors in mouse retina, and show that rods can drive visual responses in photopic conditions.

Solid state Pt(II)-pincer complexes exhibiting vapochromic responses show promise for chemical sensing applications, but their slow responses typically limit their utility. Here, Raithby and colleagues design a Pt(II)-pincer complex with a subsecond, highly-selective vapochromic response to water and methanol.

Pancreatic cancer remains difficult to treat mainly due to the drug delivery challenges posed by a strong stromal component. Here the authors develop nanocarriers that improve drug delivery efficiency and engage the host immune system against the tumor resulting in reduction of tumor growth and metastasis.

β1-adrenergic receptors are expressed in cardiac tissue and stimulated by the sympathetic nervous system. Here, the authors use NMR spectroscopy to unravel the conformational diversity upon β1-adrenergic receptor activation and provide structural insights into partial agonism and basal activity.

While non-caloric artificial sweeteners (NAS) are used as food additives, it’s unclear whether animals perceive NAS as positive or negative percept. Here, Musso and colleagues show in Drosophila that NAS is a negative percept, encoded in a new type of memory.

Singlet oxygen is known to react with carbon–carbon double bonds. Here, the authors show the unusual functionalization of α-ethereal C–H bonds mediated by singlet oxygen under mild conditions to afford lactones and hydroperoxide products.

T cell receptors are generated by somatic gene recombination, and are normally selected against autoreactivity. Here the authors show that CD4 T cells from patients with autoimmune type 1 diabetes have shorter TCRβ sequences, broader repertoire diversity, and more repertoire sharing than those from healthy individuals.

Hypoxia is a hallmark of many diseases including cancer and ischemia, and detection can be invasive and of low resolution and specificity. Here the authors show a hypoxia probe that converts non-ionizing light to ultrasound, which enables the acquisition of high-resolution 3D images in deep tissue.

Real-world surfaces exhibit spatially varying wettability, which affects water repellency and droplet behaviour on such surfaces. Here, the authors use scanning droplet adhesion microscopy to create wetting maps that visualize variations in wettability with a spatial resolution down to 10 μm.

T-UCRs encode long non-coding RNAs implicated in human carcinogenesis, but the underlying mechanisms are poorly understood. Here, the authors identify uc.339 as an oncogene in lung cancer that is upregulated through the loss of TP53 and promotes Cyclin E activation by entrapping regulatory miRNAs.

It is thought that the hospital environment may contribute to infant microbiome development. Here, Brooks et al. present a genome-resolved metagenomic study of microbial genotypes from the infant gut and from neonatal intensive care unit rooms, showing that some strains are found in both infants and rooms.

STIM proteins sense Ca2+ depletion in the ER and activate store-operated Ca2+-entry (SOCE) in response, a process associated with dendritic cell functions. Here the authors show STIM1 is the major isoform controlling SOCE in mouse dendritic cells and provide a mechanism for its requirement in antigen cross-presentation.

Learning about a rewarded outcome is complicated by the fact that a choice often incorporates multiple features with differing association with the reward. Here the authors demonstrate that feature-based learning is an efficient and adaptive strategy in dynamically changing environments.

There is a need for improved in vitro models of host-microbe interactions in the lung. Here, Barkal et al. present a microscale organotypic model of the human bronchiole for studying pulmonary infection, including volatile compound communication between microbial populations and host cells.

Elevated intraocular pressure (IOP) is a heritable risk factor for primary open angle glaucoma. Using forward mouse genetics, cell biology, pharmacology and human genetic data, the authors identify CACNA2D1 as an IOP risk gene that can be therapeutically targeted by the drug pregabalin in animal models.

Activated PI3K causes cancer, but the role of active PI3K mutations in early stages of malignancy are unclear. Here, the authors show in a mouse model that active PI3K induces centrosome amplification via AKT, ROCK, CDK2/Cyclin E and nucleophosmin, and increased tolerance of genome doubling.

Conventional grain growth models assume the velocity of a grain boundary is proportional to its curvature but cannot account for the many deviations observed experimentally. Here, the authors present a model that connects grain growth directly to the disconnection mechanism of grain boundary migration and can account for these deviations.

High dose IL-2 is a viable treatment option for cancer immune therapy, but the underlying mechanism for the accompanying undesirable morbidity is unclear. Here the authors show, using human immune system mouse models, that regulatory T cells and their functions on effector T cells are essential modulators of the related pathogenesis.

Dye-sensitized solar cells rely on molecular dyes to absorb light and conduct electrons. Parlane et al. show that weak forces such as hydrogen bonding can be responsible for the dye regeneration step of solar cells and have an impact on the photovoltage and the efficiency.

Winged radio galaxies possess wing features detectable at radio wavelengths, yet the physical interpretation of such extragalactic radio sources remains elusive. Here, the authors report the observation of a downsized Z-shaped radio emission from the Galactic microquasar GRS 1758-258, shedding light on the formation of wings in radio galaxies given its strongly reminiscent winged morphology.

The authors use an integrative clustering approach to identify two laryngeal cancer clusters with distinct prognosis and show that mutations damaging the NSD1 and NSD2 methyltransferases segregate to the cluster with favorable prognosis, and independently predict longer survival in patients with laryngeal, but not other head and neck cancers.

Block copolymers that form nanodomains and are used in nanolithography usually do not form nanopatterns with multiple shapes. Here the authors report a block copolymer that allows for UV- induced cleavage of one arm and demonstrate the transformation of the cylindrical to the lamellar nanodomain.

A cognitive map of space must integrate allocentric cues such as head direction (HD) with various egocentric cues. Here the authors report that anterior thalamic (ADn) neurons encode a pure HD signal, while neurons in post-subiculum represent a conjunction of HD and egocentric cues such as body posture with respect to environment boundaries.

Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down the extracellular matrix and recruiting endogenous cells.

Heteroatom-rich organoboron compounds are promising modulators of enzyme activity. Here, the authors report a library of aminocyanoboronates as serine hydrolases inhibitors with the most potent compound showing in vivo and in vitro nanomolar activity and high selectivity towards human ABHD3 hydrolase.

Following a large caldera creating volcanic eruption, caldera resurgence may occur as magma accumulation takes place, but this rarely leads to another a major eruption. Here, the authors using thermal and experimental models show that caldera resurgence is driven by magma viscosity contrasts.

The interrogation of enzyme activity involves the ensemble averaging of many cells, loss of spatial relationships and is often biased to abundant proteins. Here the authors develop activity-dependent proximity ligation to quantify enzyme activity at the cellular and sub-cellular level in relevant biological contexts.

The endoplasmic reticulum (ER) and lysosome are central to cellular stress responses, but it is unclear how ER stress is signaled to lysosomes. Here the authors show that ER stress activates chaperone-mediated autophagy (CMA) via direct phosphorylation of the CMA receptor LAMP2A by the lysosomal p38 MAPK.

Notch receptors can exert different roles in cancer. In this manuscript, the authors reveal that Notch1 activation and EMT promote tumor initiation and cancer cell heterogeneity in squamous cell carcinoma, while the repression of Notch3 by ZEB1 limits Notch1-induced differentiation, permitting Notch1-mediated EMT.

The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.

Low magnesium mobility in solids represents a significant obstacle to the development of Mg intercalation batteries. Here the authors show that substantial magnesium ion mobility can be achieved in close-packed ternary selenide spinel materials.

Organic materials that support both electronic and ionic transport hold promise for applications in bioelectronics and energy storage. Here, Inal et al. use transistors to quantify the materials performance of organic mixed conductors in terms of the product of charge mobility and volumetric capacitance.

Small-area mesa structures made of layered Bi-2212 cuprates should have many advantages as terahertz oscillators but experimental realization of such oscillators has proven difficult. Here the authors report Josephson emission from small-but-high mesas, achieving a broad frequency span of 1–11 THz.

Target of rapamycin (TOR) kinase operates within two distinct multiprotein complexes named TORC1 and TORC2. Here the authors report a cryo-EM structure of TORC2, establish its subunit organization, providing a rationale for TORC2’s rapamycin insensitivity and the mutually exclusive inclusion of Avo3/Rictor or Raptor within their respective TOR complex.

KCNQ1 is a voltage-gated potassium channel that is important in cardiac and epithelial function. Here the authors present a mechanism for KCNQ1 activation and inactivation in which voltage sensor activation promotes pore opening more effectively in the intermediate open state than the fully open state, generating inactivation.

Cas9 and Cpf1 have both been adapted for genome engineering, editing and gene expression regulation. Here the authors design a fusion guide RNA that can interact with both proteins for multiple and orthogonal genome manipulation.

Some bacteria can use inorganic phosphite and hypophosphite as sources of inorganic phosphorus. Here, the authors report crystal structures of the periplasmic proteins that bind these reduced phosphorus species and show that a P-H…π interaction between the ligand and binding site determines their specificity.

Fused N-heterocycles are structural motifs observed in natural products and bioactive compounds. Here, the authors developed divergent copper- and gold-catalyzed oxidative cyclizations of diynes to two types of tricyclic N-heterocycles and rationalized the product selectivity by theoretical calculations.

Primase is the specialised DNA-dependent RNA polymerase responsible for the initiation of DNA synthesis during DNA replication. Here the authors use a structural biology approach to identify the initiation site in the S. solfataricus PriSLX primase and to demonstrate that its Fe-S cluster is dispensable for primer synthesis.

Heligmosomoides polygyrus can activate mammalian TGF-β signalling pathways, but how it does so is not known. Here the authors identify and isolate a H. polygyrus TFG-β mimic that can bind both mammalian TGF-β receptor subunits, activate Smad signalling and generate inducible regulatory T cells.

During glacial periods the oceans stored carbon removed from the atmosphere, yet identifying precisely where that storage occurred remains challenging. Here, the authors show that the deep equatorial Pacific Ocean was a reservoir for respired carbon during glacial periods for at least the last 350 kyr.

The transmembrane receptor integrin is activated by talin, but so far it has remained elusive how talin is recruited to the plasma membrane. Here, the authors identify the Rap1-mediated membrane-targeting mechanism for talin, present the Rap1b/talin-F0 structure and show that talin is a direct Rap1b effector.

Formation of the vascular lumen initiates the blood flow and it is crucial for tissue homeostasis. Here, Li et. al show that the R-Ras-Akt signaling axis is crucial for reparative angiogenesis in mice because it stabilizes the microtubule cytoskeleton in endothelial cells to promote endothelial lumen formation.

Exploring the helicity-orbital coupling induced skyrmion properties is essential for the spintronic applications. Here the authors report the current controlled skyrmions and antiskyrmions dynamics with locking-unlocking helicity in frustrated magnets by including the dipole-dipole interaction in their model.

China has entered a new normal phase of economic development with a changing role in global trade. Here the authors show that emissions embodied in China’s exports declined from 2007 to 2012, while developing countries become the major destinations of China’s export emissions.

Tumors often develop resistance to radiotherapy. Here the authors show that irradiation leads to a CCR2-dependent infiltration by myeloid derived suppressor cells that promote radio-resistance through inhibition of adaptive immune responses and that the use of CCR2 antibodies in mice reduces such resistance.

The Labrador Sea drives the circulation of warm water around the North Atlantic’s subpolar gyre, yet the effect it has on European climate remains unclear. Here, the authors present a highly-resolved 3000 year-long reconstruction of gyre strength, and link gyre weakening to European cold periods.

Glucocorticoid reduces inflammation by both inducing anti-inflammatory genes and suppressing pro-inflammatory genes, but how these two functions are dictated is unclear. Here the authors show that phosphorylated glucocorticoid receptor-interacting protein 1 (GRIP1) serves as a coactivator for this response in macrophage.

Exploring the plasma processes in the pre-plasma state that lead to instabilities is challenging. Here the authors probe the evolution of the plasma phase change and the instabilities in plasma created by an exploding copper wire in Z-pinch geometry using shadowgraphy.

Neuroendocrine differentiation of epithelial tumor cells can contribute to cancer cell resistance and survival. Here, the authors show that dysregulated c-Myc promotes neuroendocrine differentiation in pancreatic ductal adenocarcinoma, leading to poor survival and chemoresistance.

Single cell profiling yields high dimensional data of very large numbers of cells, posing challenges of visualization and analysis. Here the authors introduce a method for analysis of mass cytometry data that can handle very large datasets and allows their intuitive and hierarchical exploration.

The transplantation of tissue-specific progenitor cells may be an approach in organ regeneration. Here the authors show that the nephron progenitor population of a developing mouse kidney, when ablated, can be replaced by exogenously supplied rat nephron progenitors, generating interspecies nephrons.

Using CRISPR to write specific genetic sequences can sometimes be difficult due to the preference of mammalian cells to repair breaks using NHEJ. Here the authors form nanoparticles to localize the template sequence to the nuclease, shifting repair in favor of HDR.

Nearly all atmospheric aerosols contain surface-active organic compounds; however, the nature of how they arrange remains poorly understood. Here, the authors show that fatty acids in atmospheric aerosol proxies self-assemble into highly ordered, viscous 3D nanostructures that undergo changes upon exposure to humidity and ozone.

Targeted delivery of immunomodulatory compounds to defined subsets of endogenous immune cells may improve the efficacy of combination immunotherapies. Here, the authors use PD-1-targeting nanoparticles containing a TGFβ inhibitor or a TLR7/8 agonist to deliver these payloads to T cells or via T cells to the tumor microenvironment, respectively, leading to anti-tumor efficacy in vivo.

Numerical simulation of light propagation through 1D atomic systems in the many-body limit rapidly saturates hardware capabilities. Here, the authors tackle the problem by mapping the dynamics to an open 1D interacting spin system and solving it using the matrix product state ansatz.

An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.

Coronaviruses have a relatively high mutation rate, potentially allowing fast adaptation to changing pressures. Here, Wong et al. provide the structure of the receptor-binding domain (RBD) of the human coronavirus HCoV-229E and its receptor and analyze the evolution of the RBD over the past 50 years.

The ability to quantify the organization of cell membrane molecules is limited by the density of labeling and experimental conditions. Here, the authors use super-resolution optical fluctuation (SOFI) for molecular density and clustering analyses, and investigate nanoscale distribution of CD4 glycoprotein.

Drosha and DGCR8 constitute the core Microprocessor complex, which processes primary microRNAs (pri-miRs) into mature microRNAs. Here the authors show that heme is essential for the proper processing of pri-miRs by Drosha-DGCR8, and the molecular mechanism by which heme enhances processing fidelity.

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